The transcriptomic evolution of mammalian pregnancy:gene expression innovations in endometrial stromal fibroblasts

The endometrial stromal fibroblast (ESF) is a cell type present in the uterine lining of therian mammals. In the stem lineage of eutherian mammals, ESF acquired the ability to differentiate into decidual cells in order to allow embryo implantation. We call the latter cell type “neo-ESF” in contrast to “paleo-ESF” which is homologous to eutherian ESF but is not able to decidualize. In this study, we compare the transcriptomes of ESF from six therian species: Opossum (Monodelphis domestica; paleo-ESF), mink, rat, rabbit, human (all neo-ESF), and cow (secondarily nondecidualizing neo-ESF). We find evidence for strong stabilizing selection on transcriptome composition suggesting that the expression of approximately 5,600 genes is maintained by natural selection. The evolution of neo-ESF from paleo-ESF involved the following gene expression changes: Loss of expression of genes related to inflammation and immune response, lower expression of genes opposing tissue invasion, increased markers for proliferation as well as the recruitment of FOXM1, a key gene transiently expressed during decidualization. Signaling pathways also evolve rapidly and continue to evolve within eutherian lineages. In the bovine lineage, where invasiveness and decidualization were secondarily lost, we see a re-expression of genes found in opossum, most prominently WISP2, and a loss of gene expression related to angiogenesis. The data from this and previous studies support a scenario, where the proinflammatory paleo-ESF was reprogrammed to express anti-inflammatory genes in response to the inflammatory stimulus coming from the implanting conceptus and thus paving the way for extended, trans-cyclic gestation

Hypertension in urban slums of southern India: Burden, awareness, health seeking, control and risk factor profile

Introduction: Hypertension is the leading risk factor for global disease burden. Inequalities in health among urban poor and non-poor is a matter of concern. The current study was done to estimate the prevalence of hypertension and to describe the health seeking and risk factor profile of people with hypertension in the urban slums of Kochi, Kerala, India. Methods: Blood pressure of 5980 adults from 20 randomly selected slums were measured by door to door survey by trained nurses as a part of baseline assessment for a cluster randomised controlled trial. Results: Prevalence of hypertension was found to be 34.8% (95% CI 33.5–34.9). Among those with hypertension, 66.9% were aware of their hypertensive status, of which 75.8% were initiated on treatment for hypertension. Proportion of hypertensive in the population who had their blood pressure under control was 24.5%. Among hypertensive, 53% were obese, 25.1% had diabetes mellitus, 14% had history of hospitalisation for high blood pressure. Of them, 60.3% had a per capita salt consumption above 8 g/day and 47.5% of them reported sitting for more than 8 h on a usual day. Mean monthly out of pocket expenditure for treatment of hypertension was $9(Median$8, IQR $16). Conclusion: One in three adults in urban slums of Kochi had hypertension. High rates of obesity, salt intake, physical inactivity prevails among the people with hypertension. Awareness, treatment initiation and control rate of hypertension are lower in urban slums as compared to non-slum urban areas. Slums require additional attention to ensure equitable and universal access to hypertension control

Lower PDL1, PDL2, and AXL Expression on Lung Myeloid Cells Suggests Inflammatory Bias in Smoking and Chronic Obstructive Pulmonary Disease.

Lung myeloid cells are important in pulmonary immune homeostasis and in the pathogenesis of chronic obstructive pulmonary disease (COPD). Multiparameter immunophenotypic characterization of these cells is challenging because of their autofluorescence and diversity. We evaluated the immunophenotypic landscape of airway myeloid cells in COPD using time of flight mass cytometry. Cells from BAL, which were obtained from never-smokers (n = 8) and smokers with (n = 20) and without (n = 4) spirometric COPD, were examined using a 44-parameter time of flight mass cytometry panel. Unsupervised cluster analysis was used to identify cellular subtypes that were confirmed by manual gating. We identified major populations of CD68+ and CD68- cells with 22 distinct phenotypic clusters, of which 18 were myeloid cells. We found a higher abundance of putative recruited myeloid cells (CD68+ classical monocytes) in BAL from patients with COPD. CD68+ classical monocyte population had distinct responses to smoking and COPD that were potentially related to their recruitment from the interstitium and vasculature. We demonstrate that BAL cells from smokers and subjects with COPD have lower AXL expression. Also, among subjects with COPD, we report significant differences in the abundance of PDL1high and PDL2high clusters and in the expression of PDL1 and PDL2 across several macrophage subtypes suggesting modulation of inflammatory responses. In addition, several phenotypic differences in BAL cells from subjects with history of COPD exacerbation were identified that could inform potential disease mechanisms. Overall, we report several changes to the immunophenotypic landscape that occur with smoking, COPD, and past exacerbations that are consistent with decreased regulation and increased activation of inflammatory pathways